Devices and techniques for light-mediated stimulation of trabecular meshwork in glaucoma therapy

ABSTRACT

An apparatus and technique for transscleral light-mediated biostimulation of the trabecular plates of a patient&#39;s eye in a treatment for glaucoma or ocular hypertension. The apparatus includes; (i) a working end geometry for contacting the anterior surface of the sclera and cornea to insure that a laser emission reaches the trabecular meshwork from a particular location on the anterior surface of the sclera, (ii) a laser energy source providing a wavelength appropriate for absorption beneath the anterior scleral surface to the depth of the trabecular plates, and (iii) a dosimetry control system for controlling the exposure of the laser emission at the particular spatial locations. The device uses a light energy source that emits wavelengths in the near-infrared portion of the spectrum, preferably in the range of about 1.30 μm to 1.40 μm or from about 1.55 μm to 1.85 μm. The depth of absorption of such wavelength ranges will extend through most, if not all, of the thickness of the sclera (750 μm to 950 μm). In accordance with a proposed method of trabecular biostimulation, the targeted region is elevated in temperature to a range between about 40° C. to 55° C. for a period of time ranging from about 1 second to 120 seconds or more.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a Continuation of U.S. patent applicationSer. No. 09/102,533 filed Jun. 22, 1998 titled “Devices and Techniquesfor Light-Mediated Stimulation of Trabecular Meshwork in GlaucomaTherapy.”

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to the field of medicaltherapeutics and more specifically relates to the field of glaucoma andocular hypertension therapy utilizing novel instruments and techniquesfor opto-thermal mediation of a patient's trabecular meshwork forenhancing the mitotic rate of endothelial meshwork cells and forreduction of biostructural laxity within the meshwork, which meshworkbiocharacteristics may be subject to cell-division inhibitions and/orother degradations.

[0004] 2. Description of the Related Art

[0005] Glaucomas comprise a group of debilitating eye diseases that arethe leading cause of blindness in the United States and around theworld. The pathophysiological mechanisms of glaucomas are not fullyunderstood. The principal sign of the disease is elevated intraocularpressure (IOP). Such elevations of IOP ultimately can cause damage tothe optic nerve head and result in impairment to, or loss of, normalvisual function. It is known that elevated IOP is caused by an excess offluid or aqueous AQ within the eye, which is continually produced by theciliary body CB and drained through the trabecular meshwork M to leavethe eye or globe 5 (see FIGS. 1A-1D). The excess intraocular fluidgenerally results from blockage or impairment of the normal drainagefrom the anterior chamber AC via the trabecular meshwork M. The meshworkconsists of about 10 to 25 layers of perforated trabecular plates (TP₁ .. . TP_(n)) or sheets around the filtration angle FA of the anteriorchamber AC, having a width of about 1,000 μm to 1,500 μm (1.0 mm. to 1.5mm.) in a circumference ranging from 35,000 to 40,000 μm. FIGS. 1A-1Bshow electron micrographs of trabecular plates TP with FIG. 1B includinga representation of an endothelial cell layer EC of trabecular beam Bwith the beam core BC believed to be predominantly collagen and GAGs(glucosaminoglycans) or ground substance. FIG. 1C illustrates that eachsuccessively deeper plate (more anterior plate) of the meshwork M hassmaller perforations PF or openings between the beams B than moreexposed (posterior) trabecular plates. Further, the intraplate spacingIPS diminishes with the successively deeper plates (FIG. 1C). Themeshwork M thus serves as a filtration mechanism wherein cellulardetritus, etc. in the aqueous outflow is captured before it passes intoSchlemm's canal SCH where the aqueous is transported away form the eye(FIG. 1D). The meshwork M lies about 750 μm to 950 μm beneath theanterior surface of the sclera SC.

[0006] A number of ophthalmic disease conditions are related to thetrabecular meshwork and can be linked to distinct processes orpathological conditions within a patient's eye. Any disease of thetrabecular meshwork shares the characteristic of elevating IOP. Chandleret al. described many forms of glaucoma, the principal ones being:primary open-angle glaucoma (POAG); progressive low-tension glaucoma;pigment dispersion and pigmentary glaucoma; angle-closure glaucoma;combined open-angle and angle-closure glaucoma, exfoliation andopen-angle glaucoma; angle-closure glaucoma due to multiple system cystsof iris and ciliary body; angle-closure glaucoma secondary to occlusionof the central retina vein; angle-closure glaucoma secondary tobilateral transitory myopia; ghost-cell glaucoma; lens-induced glaucoma;glaucoma due to intraocular inflammation; neovascular glaucoma; glaucomaassociated with extraocular venous congestion; essential atrophy of theiris with glaucoma. among others. (Chandler, et al., Glaucoma, 3^(rd)Ed., Lea & Febliger, Phila. (1986)) In all of the above-listed glaucomasyndromes, elevated IOP results from an increase in resistance toaqueous humor outflows through the trabecular meshwork.

[0007] In terms of incidence, primary open-angle glaucoma (POAG) is themost prevalent form of the disease affecting up to 0.5% of thepopulation between ages of 35 to 75. The incidence of glaucoma riseswith age to over 6% of the population 75 years are older. Oneidentifiable component of the POAG syndrome is the loss of endothelialcells within the meshwork which is associated with a degeneration of thenormal trabecular biostructure. It is known that the human aging processitself leads to a progressive loss of trabecular endothelial cells ECwhich compromises normal aqueous outflows therethrough. When examined intissue cultures, degraded endothelial tissue from POAG patients appearssimilar to that of “aging” individuals.

[0008] Other characteristics believed common to POAG (as well as manyother glaucomas listed above) relate to a biostructural obstructivesyndrome of the trabecular plates TP, for example, resulting fromcompression of the plates into a matt-like form that reduces intraplatespacing IPS (FIG. 1C). This factor reduces the capacity of the meshworkto act as a filtering mechanism and may develop after the meshwork isclogged with cellular detritus, pigments, etc. Such an obstructivesyndrome, it is believed, also is characterized by increased laxity ofthe trabecular beams B allowing their collapse which thus reducesintraplate spacing. The most likely causes of the meshwork degradationsdescribed above may be cumulative stresses from various factors (e.g.,oxidative, phagocytic, glucocorticoidal stresses). The fact thatincreased outflow resistance appears in the non-glaucoma “aging”population further suggests that both trabecular endothelial cellularprocesses and an obstructive meshwork syndrome play significant roles indecreasing aqueous outflows.

[0009] The normal IOP for humans usually ranges from about 10 to 22 mm.Hg. (1.3-2.7 kilopascals) and is maintained by a balance in the aqueousproduction by the ciliary body CB, inflows to the anterior chamber ACand outflows therefrom. As described above, in a normal eye, the aqueousdrains from the anterior chamber through the meshwork into Schlemm'scanal SCH, through which it leaves the eye. In patients in a glaucomousstate, besides passing through Schlemm's canal, the aqueous may alsopass through the ciliary muscle CM into the suprachoroidal space andfinally leave the eye through the sclera SC (FIG. 1D).

[0010] For purposes of description, the intraocular pressure (IOP) in ahuman can be defined by a formula of the following type:

IOP=P _(e)+(F _(t) −F _(uv))×R:(TM _(cep) ,TM _(sp) ,TM _(br))

[0011] where P_(e) is the episcleral venous pressure (generally regardedas being around 9 mm. Hg.); F_(t) is the total outflow of the aqueoushumor from the anterior chamber, F_(uv) is the fraction of aqueouspassing by the uveoscleral route; R is the resistance to outflow ofaqueous through the trabecular meshwork into Schlemm's canal, which canbe considered to be functionally related to (i) the vitality oftrabecular endothelial cellular cellular and enzymatic processes(TM_(cep)), (ii) the dimensions of intraplate spacing between (TM_(ips))relative to a norm, and (iii) the trabecular beam resiliency (T_(br)) orbiostructural tension within the meshwork under the pressure of aqueousoutflow therethrough. Such a formula is useful for understanding thetargets of various prior art therapies, if not for use as an actualmathematical model.

[0012] Among several therapies targeted at various elements of the aboveequation, two forms of treatment are common: (i) medical or drugtherapies, and (ii) trans-corneal laser irradiation of the trabecularmeshwork via a goniolens (see FIG. 2A). In medication therapies, theobjective may be to lower IOP by either of several routes: reducing theaqueous flow total (F_(t) in the above equation); increasing uveoscleralflow (F_(uv) in above equation); or altering resistance to outflow (R),by stimulating endothelial cellular processes (TM_(cep)) which isbelieved to act on outflow resistance. Drug therapies have thedisadvantages of requiring a lifelong treatment; causing significantside effects; being very costly (between $1,000-$2,000/yr.); and beingunavailable or unaffordable in lesser developed countries of the worldwhere the incidence of glaucoma is highest.

[0013] In the laser therapies, ALT (argon laser trabeculoplasty) and SLT(selective laser trabeculoplasty) have been developed which both rely ona trans-corneal approach to the posterior surface of the meshwork.Introduced in the 1980's, ALT uses an argon laser operating at awavelength (λ) of 488 nm to 514.5 nm with a long pulse duration of about0.10 second and a power range of from 500-1000 mW to irradiate a seriesof about 50 spots only around the 180° of the meshwork (see FIG. 2A). InALT, the ophthalmologist utilizes a goniolens to direct laser beamstrikes on the exposed surface of the trabecular plates TP. Thecausative mechanisms of ALT have never been clearly understood. It hasbeen proposed that each ALT beam's incidence on the meshwork causes aburn or a melt and results in the formation of scar tissue thatcontracts (or tensions) a portion of the meshwork around the burn (cf.TM_(br) or resiliency of beam B in above formula). According to anotherview, the ALT meshwork burns cause a wound healing response resulting insignificant cell division and the transient repopulation of endothelialmeshwork cells, at least in zones around the burns (cf. TM_(cep) above).FIG. 2B shows an electron micrograph of an ALT meshwork burn indicatedat 6, which may tension the meshwork at the burn periphery indicated at7. A principal disadvantage of ALT is that it can only be performedtwice on an eye—once in the superior (or nasal) 180 degrees of themeshwork and once in the inferior (or temporal) 180 degrees. The lasermelts are too significant to repeat the treatment in the same portion ofthe meshwork.

[0014] The more recently developed trans-corneal laser approach is SLT,which uses a short-pulse, frequency-doubled, 530 nm Nd:YAG laser withpulse duration of 3 nanoseconds and energy levels that range from 0.60mJ to 1.20 mJ. The SLT modality is called “selective photothermolysis”by its inventor (Dr. M. Latina) wherein the proposed wavelength isabsorbed by endogenous pigment within the meshwork which kills (orlyses) the pigmented cells without damaging the non-pigmented cells (seeU.S. Pat. No. 5,549,596). In theory, the short pulses allow heat todissipate from the absorbing pigmented cells before killing adjacentcells (see FIG. 3). The SLT inventor proposes that the causativemechanisms of increasing aqueous outflows relate to (i) an inflammatoryresponse in the meshwork that results in activation of enzyme systemsthat clean up the meshwork, and (ii) a mild expansion of the meshworkplates or perforations by killing pigmented cells with a photothermal ormicrocavitation effect (FIG. 3). The following table compares the ALTand SLT parameters. Pulse Beam Treatment λ Duration Power Size Area ALT488-514.5 nm 0.1 second 500-1000 mW 50 μm 50 spots/180° SLT 530 nm   3nanoseconds 0.6-1.2 mJ 300-400 μm 50 spots/180°

[0015] Several disadvantages are associated with the ALT/SLT modalities.First, both systems approach the meshwork through the anterior chamberAC by means of a goniolens. For this reason, the wavelengths must beselected from a portion of the spectrum that penetrates through thecornea C and aqueous AQ without the light energy being absorbed andextinguished—a distance of about 4 mm. to 8 mm. (4000 μm to 8000 μm).This factor greatly limits the choice of possible wavelengths—each ofwhich has a different absorption coefficient in water (see FIG. 4A). Therequirement of using a goniolens along with a laser aiming beam alsomakes the ALT/SLT approach technique dependent—making the therapyavailable only to highly skilled surgeons.

[0016] A second disadvantage the ALT/SLT modalities relates to the lackof exact understandings of the causative mechanisms for improvingoutflow facility. Since ALT has effects that last for about 5 years atmost—and can be repeated only once—the medical and surgical communitieshave not developed a consensus about sequencing medical and surgicaltherapies. Glaucoma is a disease state that requires lifelongmanagement. Some physicians propose that ALT be resorted to only afterdrug therapies have lost their effectiveness; other physicians proposeALT as a first line of defense in order to delay a lifetime of drugtherapy and the attendant side effects.

[0017] Other significant disadvantages of ALT/SLT relate to the factthat both deliver similar photothermal effects to a limited depth withinthe trabecular plate structure. That is, the ALT/SLT causativemechanisms—no matter what they are—probably only operate within thetrabecular plates TP most exposed to the incident beam which thus absorbthe beam's photonic energy. This factor suggests that only the first fewplates (most posterior plates) exposed to the anterior chamber AC areaffected by such energy delivery—perhaps only about 10%-20% of thelarger dimensioned trabecular plates. It is postulated that theunderlying (anterior) trabecular plates that have smallest dimensionedperforations PF and the least intraplate spacing IPS are degraded to thegreatest degree and thus play the most significant role in increasingIOP by clogging the pathways to Schlemm's canal (see FIG. 1D). Yet,these most anterior meshwork regions probably remain untreated by ALTand SLT.

[0018] Further, studies have shown that ALT is not effective in allpatients, and actually increases IOP in over 20% of patients.Additionally, in recent SLT patients, the following complications havebeen documented: uveitis in the form of iritis in virtually all treatedeyes; corneal burns in up to 25% of treated eyes; and anterior synechiaeor adhesions due to the significant absorption of light energy in thepigmented cells of the meshwork.

[0019] What is needed is an improved technique for effectingbiostructural changes in the trabecular meshwork to facilitate aqueousoutflows that provides: (i) means for stimulating endothelial celldivision to cause cell repopulation and rejuvenation within thetrabecular plate structure; (ii) means for inducing a slightinflammatory or wound healing response to activate enzymatic systemssuch as stromolysin and metalloproteases that may help clean up themeshwork; (iii) means for causing the desired biostimulative effectswithout photocoagulation, photodisruption or photothermolysis ofendothelial layers of the meshwork as in ALT/SLT; (iv) MIS (minimallyinvasive surgical) means for causing the desired effects in a repeatablemaintenance therapy that can continue over the lifetime of the glaucomapatient; (v) MIS means for meshwork treatment that can be evaluated inall patients before resorting to drug therapies; (vi) MIS means fortreating 360° of the meshwork instead of 180° or less; (vii) means forcausing the desired effects substantially equally on all trabecularplates from the most posterior to the most anterior, (viii) MIS meanssimultaneous treatment of a substantial arc of the meshwork with adevice in a single treatment position rather than time-consumingtreatment in a series of spots; (ix) MIS means for biostimulating thetrabecular structure in the many forms of glaucoma (other than POAG)that are not possible with a goniolens and laser strikes through theanterior chamber, (x) MIS means for treating the meshwork without riskof any corneal burns; and (xi) MIS means for treating the trabecularstructure that is not technique-dependent and capable of being performedby optometrists or other lesser-skilled health care professionals in thelesser developed countries of the world.

SUMMARY OF THE INVENTION

[0020] The laser system and handpiece of the present invention areparticularly adapted for use in elevating the temperature of a patient'strabecular meshwork for purposes of stimulating cellular processes. Thesystem is adapted for a novel transscleral approach (instead oftrans-corneal) and is called opto-thermal transscleral trabeculoplasty(or OT³). The present invention provides cooperating means to developbiostimulative opto-thermal effects in a patient's trabecular meshwork,including a working face for contacting the sclera and aligning the axesof a plurality of beams' propagation toward the meshwork, and a laserenergy source having a wavelength range appropriate for penetration tothe meshwork. Further, the invention includes an optional dosimetrycontrol system for terminating or controlling energy delivery based onfeedback signals from a temperature sensor array in the working face.

[0021] The working face has a 1^(st) corneo-spherical receiving portionand a 2^(nd) sclero-spherical receiving portion for positioning the facein contact with the globe with a footprint dimension that is largeenough to stabilize the working face at a proper treatment angle. Withinthe working face are a plurality of light beams emitters connected withfiber optics to the laser source. The emitter axes at which the beamspropagate are provided at a predetermined angle relative to the 1^(st)and 2^(nd) part-spherical receiving portions of the working face, forexample a tangent to the sclera.

[0022] Research and modeling indicates that the preferred wavelengthranges for opto-thermal biostimulation of the trabecular plates lie inthe near-infrared portion of the spectrum, preferably in ranges of about1.30 μm to 1.40 μm or about 1.55 μm to 1.85 μm. It is believed thatabsorption coefficients related to the above ranges, or a subset of thesuch ranges, will prove best suited for such trabecular meshworkstimulation. The depth of absorption of such wavelength ranges willextend through most, if not all, of the thickness of the sclera (750 μmto 950 μm). For the proposed method of trabecular biostimulation, thetargeted region is elevated in temperature to a range between about 40°C. to 55° C. for a period of time ranging from about 1 second to 120seconds or more. More precisely, the desired range would be betweenabout 40° C. to 50° C. for such time periods. The optimal therapeuticeffects will result from a balance of appropriate light energywavelength, power level, exposure duration, together with the thermalabsorption characteristics of the heat-sink working face.

[0023] The light-mediated trabecular biostimulation techniques proposedherein differ greatly from other common laser-tissue interactions. Theproposed technique develops only low energy densities in the absorbingmedium as can be seen in the chart of FIG. 4C where various temperaturelevels indicate different effects on tissue. Such biostimulative effectsare caused by a photoexcitation modality proposed herein which differssignificantly from typical modalities of laser-tissue interactions: thephotocoagulation and photodisruption modalities. In the photocoagulationmodality, photons elevate tissue temperatures sufficient to coagulate,denature, shrink, desiccate or cause thermolysis of tissues such as inALT and SLT (see FIG. 4B). In the photodisruption modality, photons of alight energy beam disrupt the chemical bonds of atoms or moleculesmaking up the medium, with the end result being that the medium isvaporized as indicated in FIG. 4B. In the present invention, theobjective is to elevate meshwork to temperatures well below those usedto practice the photodisruption or photocoagulation modalities. Thephotoexcitation modality proposed herein uses far less energetic photonsin the above-described ranges which will cause atoms and molecules inthe meshwork or aqueous AQ engulfing the meshwork to vibrate orresonate. The excitement or resonant effect will elevate the temperaturewithin the absorbing medium (meshwork) without disrupting anyintramolecular or intermolecular chemical bonds, such as would occurtemperatures above about 60° C. which can cause denaturation of tissue.

[0024] The dosimetry control component of the invention can be adaptedto control exposure duration, power levels and timing of energy deliveryin various operational modes. A basic mode of operation can follow apre-set program of timing and power based on treatment experience. Apreferred operational mode is based on a feedback-control system thatreceives signals from a thermal sensor in the working end of the device.Another preferred operational mode is based on a feedback-control systemand a beam sequencing controller that sequences beam delivery between oramong non-adjacent emitter locations to optimize temperature elevationin the meshwork while minimizing temperature elevation in the anteriorand mid-sclera.

[0025] In general, the present invention advantageously provides asystem having an arrangement of a plurality of n spaced-apart beamemitters in a radius that corresponds to that of the trabecular meshworkof a patient's eye for transsclerally treating an angular portion of themeshwork with a single energy delivery.

[0026] The invention advantageously provides a device having a workingface with geometry and part-spherical receiving forms for receivingportions of a patient's cornea and sclera to insure the light energybeams are directed toward the trabecular plates.

[0027] The invention advantageously provides a device having n lenselements to insure that the light energy beams penetrate and areabsorbed substantially about the region of the trabecular meshwork.

[0028] The invention advantageously provides a device and method forcreating a reverse thermal gradient in the sclera by lowering thetemperature of the anterior surface of the scleral with a heat-sinkworking face to protect the scleral epithelium.

[0029] Additional features and advantages of the device and method ofthe present invention will be understood from the following descriptionof the preferred embodiments, which description should be taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030]FIGS. 1A is an electron micrograph of the trabecular meshwork of apatient's eye.

[0031]FIG. 1B is an enlarged electron micrograph of the trabecularmeshwork of FIG. 1A with a schematic sectional view of a trabecularbeam.

[0032]FIG. 1C is a sectional representation of the trabecular platelayers of meshwork of FIG. 1A.

[0033] FIGS. 1D-1E are sectional views of a patients' eye or globeshowing the location of the trabecular meshwork.

[0034]FIG. 2 is a view of a prior art method of laser treatment oftrabecular plates.

[0035]FIG. 2B is an electron micrograph of a laser melt of trabecularplates in the prior art method of FIG. 2A.

[0036]FIG. 3 is a schematic view of another prior art method of lasertreatment of a trabecular plate.

[0037]FIG. 4A is a graph showing light wavelengths with absorptioncoefficients in water.

[0038]FIG. 4B is a chart indicating laser-tissue effects at varioustemperature levels in tissue, including the modality of photoexcitementproposed herein; the photocoagulation modality wherein tissue is causedto coagulate, denature or shrink; and the photodisruption modalitywherein tissue is vaporized.

[0039]FIG. 5 is a perspective view of the handpiece of the presentinvention together with a block diagram of the components and controlsystems of the invention.

[0040]FIG. 6 is an enlarged perspective view of a the distal working endof the handpiece of FIG. 5 depicting a plurality of emitter locationsand light energy beams emitting therefrom.

[0041]FIG. 7 is a sectional view of the working end of FIG. 6 takenalong line 7-7 of FIG. 6 showing particular working end geometry.

[0042]FIG. 8 is a plan view of working end of FIG. 6 showing otherparticular working end geometry.

[0043]FIG. 9 is an enlarged sectional view of the working end of FIG. 7showing a lens element.

[0044]FIG. 10 is an enlarged sectional view of a sclera and cornea andshowing various transcleral angles-of-attack.

[0045]FIG. 11 is a partial sectional view of an eye showing thefootprint of the working end of FIGS. 6, 7 & 8.

[0046] FIGS. 12-12B are sectional representations of a patients scleraand trabecular meshwork regions depicting a manner of utilizing theapparatus of FIG. 5 in performing a method of the invention in elevatingthe temperature of the meshwork; FIG. 12A indicating the thermal effectof a light beams' incidence on tissue at the instant of energyabsorption; FIG. 12B indicating the thermal effect of the light beams anumber of nanoseconds later.

DETAILED DESCRIPTION OF THE INVENTION

[0047] Referring now to FIG. 5, the laser system 8 with handpiece 10 ofthe present invention is shown which is adapted for the novel techniqueof elevating the temperature of a patient's trabecular meshwork forbiostimulation purposes. The system of the invention, for convenience,may be at times referred to as an OT³ system (“OT-Cubed system”) for thepracticed technique of opto-thermal transscleral trabeculoplasty.

[0048] The present invention includes cooperating means for projectionof energy beams at particular penetration angles in particular spatiallocations on the anterior surface of the sclera, together withwavelength means for transscleral penetration of such energy beams toreach the patient's trabecular meshwork. The OT³ device thus provides(i) a working end with particular geometry for propagating light beam(s)relative to the sclera's anterior surface, (ii) a laser energy sourceoperating within selected wavelength domains, and (iii) an optionaldosimetry control system for controlling (or terminating) laser energydelivery based on a temperature feedback signals. These systems andaspects of the invention will be described in order below, andsubsequently in their use in performing the technique of the inventionin stimulating cellular and other processes of the trabecular meshwork.

[0049] 1. Working End Beam Propagation Geometry. As can be seen in FIG.5, handpiece 10 comprises a working end portion 12 that extends alongaxis 15 and which is coupled to body portion 16. The working end 12 isfabricated of any suitable transparent material, such a transparentmedical grade plastic. The body is formed of any suitable material suchas metal or plastic and is adapted for gripping with a human hand.Preferably, working end 12 and body 16 are of inexpensive and disposableinjection-molded parts. The body 16 has proximal and distal ends,indicated at 17 a and 17 b, respectively, with end 17 a having adetachable coupling 18 for connecting fiber optic cable 20 thereto foroperative connection to laser energy source 25 described below.

[0050] FIGS. 6-8 show perspective, sectional and plan views of workingface 30 of working end 12 with a plurality of emitter locations 31A-31 nand lens elements 33A-33 n from which beams 35A-35 n are be emitted. Thepreferred embodiment shows a plurality of 6 emitter locations 31A-31 n,but it should be appreciated the number of emitters may range from about1 to 10 per any 10° to 45° of radial angle distance RAD of working face30 (FIG. 8) described below (i.e., n=1 to 10). The number of emitterlocations 31A-31 n also will vary depending on selected beam diameterdescribed below. FIG. 6 shows that individual optic fibers 40(collectively) are connected by any suitable means (e.g., cement or aclamping mechanism) at each emitter location and more particularly toeach lens element 33A-33 n. FIG. 9 shows an enlarged sectional view of alens element 33A which is adapted as a plus-type lens to converge thebeam generally at depth D which is about the depth of meshwork M (about750 μm to 950 μm) as is known in the art. It should be appreciated thatthe lens element 33A is represented as a part-hemispheric lens but thatany flat field or convergent lens may be appropriate foropto-stimulation of the meshwork M and falls within the scope of theinvention.

[0051] The light beams 35A-35 n may be generated and emitted by theemitters from any suitable source of light, either coherent ornon-coherent, and may be from a pulsed or CW laser source in thewavelength domain described below. It should be appreciated that theterm “emitter” is used herein to describe the location or point at whichbeams 35A-35 n are emitted from working end 12 and lens elements 33A-33n into the sclera, and as such, the emitter is considered to be acombination of elements including, but not limited to, the laser source25 together with optics, fiber optics, lenses, mirrors, filters,splitters, combiners, energy attenuators, beam shapers and otherarrangements operatively connected between the laser source 25 and thelens elements 33A-33 n. FIG. 5 shows beam splitter 44 that is known inthe art for splitting output from one or more light sources 25 to pumpthe light energy into each individual optic fiber 40.

[0052] Turning now to FIGS. 10-11, very particular beam-anglepropagation means are formed into working face 30 of working end 12 thatcomprises a balance between several considerations and several potentialtransscleral angles-of-attack to reach the trabecular meshwork M.Referring back to FIG. 7, the working face 30 in its treatment positionis adapted to interface with globe 5 generally in surface contact withthree portions of the globe: the sclera SC, the limbus 36 and the corneaC. In other words, the working face has a first corneal-sphericalreceiving portion 45A and a second scleral-spherical receiving portion45B with annular limbus-interface portion 47 therebetween. The limbus 36herein is defined as the particular annular transition region from 0.5mm. to 2.0 mm. between the sclera and cornea. Further, the working face30 extends a minimum radial angular distance RAD when measured indegrees as will be described below (see FIG. 8). Thus, the footprintdimensions of working face are large enough to stabilize the workingface 30 against the globe, as well as for functioning as a heatsink asdescribed below.

[0053] FIGS. 10-11 show that a particular limited range ofangles-of-attack (or beam propagation) relative to anterior surface 48that is indicated to reach meshwork M. Among the considerations fordetermining the most preferable angle-of-attack are (i) the reduction ofincident beam reflection off the anterior surface 48 of the sclera SC;(ii) the reduction of unnecessary photon scattering in the mid-sclera53, and (iii) the elimination of any angle-of-attack that might alignwith anatomic structures that one would not want to irradiateunnecessarily. To meet these objectives, the working face 30 is formedwith a geometry for angular positioning the axes 50 (collectively) ofpropagation of beams 35A-35 n within a defined angle—for example angle βwhich measures the angle between an axis 50 of beam propagation and atangent T to the sclera in an incident zone Z outside the limbuscenterline 51. In other words, axis 50 extends from the zone Z in whicha light beam penetrates the anterior 48 of the sclera to hit meshwork M.As can be seen in FIG. 10, any beam propagation at other angles alongother lines (e.g., lines X₁ or X₂) that are more oblique relative totangent T may cause photonic energy to be absorbed in undesirablelocations like ciliary body CB or iris 52 and thus damage tissue outsidethe meshwork M. The correct beam propagation angle β can be defined in anumber of different geometric manners relative to surfaces, radii, axesetc. of globe 5, and for that reason the ranges of radii of curvature ofa normal globe are shown in FIG. 10. Preferably, as shown in FIG. 8,beam angle β is within a range of about 10° on either side of a linedrawn perpendicular to tangent T in the zone Z of the sclera and limbus.Incident zone Z has in lesser diameter of about 0.0 mm. to 0.5 mm. fromthe centerline 51 of limbus 36 and an outer diameter to 3.0 to 5.0 mm.from the centerline 51 of the limbus 36. Thus, the working end geometryin its “contact position” or “treatment position” against globe 5orients beams 35A-35 n to (i) allow about the least distance of travelpossible through the sclera SC to the meshwork M to correspond towavelength domains described below; (ii) allow reduction of photonscattering and heat within the mid-sclera 53 by minimizing the beams'propagation length through the sclera; and (iii) allow light beams35A-35 n delivery at close to a 90° angle relative to anterior surface48 of sclera SC to reduce surface photon reflection.

[0054] Of particular interest to the invention, the compound curvatures45A and 45B (first corneal-spherical receiving portion 45A and secondscleral-spherical receiving portion 45B) of working face 30 allow theophthalmologist to gently fit the working face against the globe 5 aboutthe corneal-scleral junction to insure the optimal beam spatial locationand beam angle-of-attack. The ophthalmologist first may move the workingface laterally back and forth as shown in arrow A1 in FIG. 10 until itfits comfortably against the eye. Thereafter, the ophthalmologist maytilt working face 30 against the curvature of the sclera and cornea asindicated by arrow A2 as shown in FIG. 10 to establish the correct angleβ relative to globe 5. In the previous view of the working face in FIG.7, it can be seen that first part-spherical receiving form 45A has ameridional or first cross-sectional radius R1 of about 6.4 mm. to 7.8mm. which represents a meridian of corneal curvature. The working face30 has second part-spherical receiving form 45B with a secondcross-sectional radius R2 of from about 8.0 mm. to 12.0 which representsa meridian of scleral curvature (or greater) with the forms 45A and 45Bmeeting along partial annular junction 47. The width of firstpart-spherical receiving form 45A may range from about 0.5 mm. to 4.0mm., indicated at W1 in FIG. 8. The width of second part-sphericalreceiving form 45B may range from about 2.0 mm. to 5.0 mm., indicated atW2 in FIG. 8.

[0055]FIG. 8 shows a plan view of working face 30 indicating that it isadapted to extend a particular angular or radial angle distance RADaround globe 5 and is shown in this preferred embodiment with a radialextension RAD of about 60° out of 360°. It should be appreciated thatother embodiments are possible and fall within the scope of theinvention and such radial extension may range between about 10° and 180°(see FIG. 8). In terms of circumferential dimensions, the dimensionalong partial annular junction 47 of working face may range from about2.5 mm. to 2.0 cm. The footprint 54 defining the surface area of workingface 30 preferably has an area of at least 20 mm.² to meet therequirements of stabilizing the working face against globe 5 to providethe correct angle of beam propagation, and to provide sufficient heatabsorption characteristics for any of the materials of working facedescribed herein. More preferably, the footprint 54 of working face 30has an area of at least 40 mm.² to meet above requirements. Still morepreferably, the footprint 54 of working face 30 has an area of at least60 mm.² to meet such requirements.

[0056] The dosimetry control system 55 will be described in detail belowin Section 3. Some aspects of the dosimetry control system can be fed bya signal from sensors 57 (collectively or sensor array) in working face30. Therefore, referring back to FIGS. 6 & 8, it can be seen that sensorarray 57 is provided which comprises thermisters or thermocouplescarried in a spaced apart relationship close to lens elements 33A-33 nin face 30. The sensors may be in actual contact with the sclera SC ormay measure the temperature of the material of face 30 that is incontact with the sclera. Each thermocouple or thermister (a temperaturesensor that has resistances that vary with the temperature level) is anysuitable type known in the art and may consist of paired dissimilarmetals such as copper and constantan which form a T-type thermocouple.

[0057] Referring back to FIG. 5, a block diagram of the controllers ofthe system 8 is included and further shows a visible aiming beam (e.g.,a HeNe laser) indicted at 58 operating at 630.8 nm or any other suitablevisible laser wavelength. The system includes dosimetry control systemindicated at 55 and optional beam sequence controller 59, which computercontrollers are adapted to operate in cooperation (as will be describedbelow) to control the power of beams 35A-35 n, as well as the timing, oflaser energy delivered from laser source 25.

[0058] 2. Laser Source Wavelength Selection. The preceding sectiondescribed the working end geometry or positioning mechanisms of thenovel OT³ device to insure that the physician can easily andconsistently locate the working face 30 in suitable “treatmentpositions” on or about the anterior scleral surface. This section andFIGS. 12A-12B describe the means provided by the invention forcontrolling penetration of light beams 35A-35 n beneath the anteriorscleral surface 48 to provide the desired photon absorption within thetrabecular meshwork M. The biostimulative effect is caused by the beam'sphotonic energy being absorbed and exciting (or vibrating) moleculeswithin the meshwork, and for that reason the energy delivery effect maybe called herein a photoexcitation modality to distinguish it fromvarious high-energy laser delivery modalities described in the sectionabove titled “Summary of the Invention”.

[0059] Turning back to FIG. 10, the perspective and partial sectionalview of globe 5 shows the beams 35A-35 n incident within zone Z at aparticular moment in time that represents a technique of the invention.FIG. 11 also shows the approximate location of zone Z over thetrabecular meshwork with the footprint 54 of working face 30 and theworking end 12 in phantom view in a second treatment location. FIG. 12Aillustrates an enlarged fill-thickness sectional view of the sclera SCand meshwork M taken along an arc-like section of FIG. 11. Sclera SC hasa number of layers including epithelial layer 60 with the total scleralthickness ranging from about 750 μm to 950 μm.

[0060] The object of the invention, transscleral opto-thermalbiostimulation, requires identification of a specific light wavelengthdomain that may be produced by laser source 25 to penetratesubstantially to the depth of about 750 μm-950 μm. As background, whenlight energy is incident upon tissue, five effects may result: (i) thebeam, or some or all of the photons thereof, may be reflected off thetissue surface; (ii) the photons thereof may be transmitted entirelythrough the tissue medium, (iii) the photons thereof may be absorbedalong the beam's propagation in the tissue medium by absorption within achromophore, (iv) the photons thereof may be absorbed along the beam'spath of propagation by varied processes of scattering; or (v) some ofbeam may be scattered within the tissue beyond the region of the beamspath as it propagates within the tissue medium.

[0061] To provide photon absorption to a depth in tissue of about 750μm-950 μm, two of the above factors are of interest to causebiostimulation of the trabecular meshwork M. Of particular interest arethe photon absorption effects (iii) and (iv) listed above. Preferably,the photons of the energy beams 35A-35 n will be absorbed by the H₂Ocontent of the meshwork acting as a chromophore, and also be absorbed byphoton scattering processes, thus elevating meshwork temperature. (Asnoted previously, photon reflection off anterior surface 48 is minimizedto the extent possible, and deeper absorption is allowed, by orientingaxes 50 of the beams substantially perpendicular to the anterior scleralsurface which relates to beam incident effect (i) above).

[0062] Since the sclera is about 75%-80% water with little or nocellular pigmentation, FIG. 4A is relevant as it depicts an absorptioncoefficient of water as a function of wavelength (λ). As can be seen inFIG. 4A, the absorption coefficient of water varies by a factor of about10,000,000 from a peak light transmission where λ=500 nm (not shown) inthe visible spectrum to peak light absorption where λ=at 2.8 μm in theinfrared portion of the spectrum. Tissue research and mathematicalmodeling of various wavelengths indicates that the preferred wavelengthrange for light-mediated meshwork biostimulation lies in thenear-infrared, the laser source 25 preferably operating at a wavelengthranging from about 1.30 μm to 1.40 μm or from about 1.55 μm to 1.85 μm.The wavelength ranges correspond to an absorption coefficient (α) in H₂Oranging between about α=2.0 cm⁻¹ to 10.0 cm⁻¹, which is similar to thesclera. Such a range of absorption coefficients would result in thephotonic energy being absorbed to a depth of about 750 μm to 1100 μm—inother words the depth of the trabecular meshwork or slightly beyond. Itis not important if the absorption is somewhat deeper than the meshwork,for the aqueous AQ will absorb or extinguish the energy beam. Unlike ALTand SLT wavelengths that are absorbed by a pigment (melanin) orchromophore in the meshwork, the proposed wavelengths rely on H₂O as thechromophore which is in the trabecular plates TP and the aqueous AQwhich allows a substantially uniform temperature elevation in the entireregion of the meshwork for biostimulation purposes.

[0063] The temperature targeted for meshwork biostimulation is in therange of about 40° C. to 55° C. for a period of time ranging from about1 second to 120 seconds, with the temperature inversely related to theduration of exposure. More preferably, the target temperature is withina range of 40° C. to 50° C. It would be preferable to achieve an energyprofile that photoexcites the region of the meshwork withoutover-elevating the temperature levels in the sclera overlying themeshwork. For example, it is preferable that the opto-thermal effects donot cause excessive cell death in epithelial layer 60 or in themid-sclera region 53. Such excessive cell death along the light beam'spropagation through the sclera could induce an inflammatory response orwound healing response which would be undesirable, although not seriousthreat to the patient's health. Cell damage in the sclera is to beexpected to some extent, but since the inventive technique istransscleral there should be few undesirable side effects. This is to becontrasted with the trans-corneal approach of SLT which causes cornealburns in significant numbers of cases resulting in at least a transienteffect on corneal clarity.

[0064] The present invention provides protection means for preventingover-elevation of temperatures in the epithelial layer 60 and themidscleral region 53, by: (i) balancing wavelength selection along witha low laser power level to penetrate the sclera; (ii) balancing exposureduration with temperature which exposure can be terminated withfeed-back control; and most importantly (iii) providing heat-absorptioncharacteristics incorporated in working face 30. In other words, atransient reverse thermal gradient in the sclera can be achieved by useof the heat-sink working face 30. Due to the relatively low targettemperatures, the heat-sink of even a plastic working face 30 around thelens elements will carry a significant amount of heat away from theanterior regions of the sclera. It should be appreciated that otherheat-sink materials known in the art may be used for portions of theworking face 30, such as sapphire, quartz or heat-absorbing ceramics(other than lens elements). FIG. 12A depicts a sectional view of thepropagation of beam 35A through the sclera exactly at the moment of itsincidence on anterior surface 48 with exemplary isotherms 70 a-70 cindicating the effects of photon absorption; FIG. 12B depicts the samescleral location in as little as several nanoseconds after energydelivery has been terminated. In particular, FIG. 12B indicates thatsubstantially all heat has been conducted away from anterior surfaceregion 48 of the sclera to the heat-sink with exemplary isotherms 70a-70 c indicating the surface cooling effect that concentratestemperature in the region of meshwork M. Such modeling shows how atransient reverse thermal gradient (cooler at anterior surface 48 thanmid-sclera 53) can be developed to cause thermal meshwork biostimulationwithout raising temperatures excessively in the anterior 48 andmid-sclera 53.

[0065] Another aspect of the OT³ system for effective biostimulation ofthe meshwork M relates the preferred diameter of scanned beams 35A-35 nto provide temperatures within the particular ranges described above.Either a CW (continuous wave) or fast pulsed laser is suitable toperform the biostimulation technique of the present invention utilizinga beam width ranging from about 25 μm to 1 mm. for reasons that can beexplained by the mechanisms of heat transfer in tissue. In the preferredwavelengths described above, when the light beam is absorbed in tissuemedium (both by chromophores and by photon scattering) the energy in thebeam is imparted to the scleral absorbing medium along the path of beampropagation. The photonic energy that is absorbed by the medium heatsthe absorbing volume instantly, for example in a period ranging fromfemto-seconds to pico-seconds. Essentially, all of the energy in thelight beam is deposited in the tissue within about one extinction length(which is directly related to the absorption coefficient a of thesclera). Thus, it can be calculated that a three-dimensional volume ofthe medium will be elevated in temperature and is dependent on (i) thebeam diameter, and (ii) the extinction length of the particularwavelength (with some adjustment for photon scattering). To optimize themeshwork biostimulation, it is necessary to deposit enough energy intothe absorbing volume to elevate the volume to the desired temperaturerange before it diffuses into surrounding tissue volumes. The process ofheat diffusion, called thermal relaxation, describes such process ofconduction and defines the absorbing volume's thermal relaxation time(often defined as the time over which photothermal temperature elevationis reduced by one-half). Such thermal relaxation time scales with thesquare of the diameter of the irradiated absorbing volume in a sphericalvolume, decreasing as the diameter decreases. For a cylindrical-shapedirradiated volume (see FIG. 12A) with diameter d and length L, suchthermal relaxation time is determined by the lesser of the twodimensions. Thus, in the laser wavelengths and tissue absorptioncoefficients described above, it is preferable to have the heat thermalrelaxation time in the anterior and mid-sclera as low as possible todiffuse and reduce temperature elevations in those regions. For thesereasons, it is postulated that beam diameters in that range of about 25μm to 1 mm. would be best suited for meshwork stimulation, with asimilar spaced-apart dimension SA from about 25 μm to 1 mm. between theindividual beams and lens elements 33A-33 n (see FIG. 6).

[0066] 3. Dosimetry Control System of OT³ Device and Methods of theInvention. The OT³ device 8 includes a dosimetry control systemindicated at 55 in FIG. 5 that is adapted to control the power level oflaser energy delivered through the emitter locations 31A-31 n in variousoperational modes. In utilizing the device of FIG. 5 to perform themethod of the invention, the ophthalmologist gently positions theworking face 30 of the device against the patient's eye as shown inFIGS. 7, 10 & 11 above following administration of a topical anesthetic.As described above, after moving the working face laterally about thesurface of globe 5 and tilting the device back and forth, the physicianwill have a tactile feel of the correct position of the working face, atwhich time he may actuate the device by means of a footpedal (not shown)or any other suitable trigger mechanism to deliver laser energy under anumber of different optional operational modes. The ophthalmologistrepeats the biostimulative treatment in successive and slightlyoverlapping location in an arc around the entire 360° of the globe. Thedosimetry control system 55 typically includes microprocessor 65together with appropriate software programs 66 and may be designed tomodulate the power level of the laser source 25 at any level among acontinuous range of power levels as the emitters project beams 35A-35 n.The software 66 that is part of the dosimetry control system, as theterm is used herein, includes a conventional software program, a programwithin a programmable chip, or any other form of algorithm carried inany form of memory storage system. Within the hardware portion ofdosimetry control system 55, there may be a keyboard, disk drive orother non-volatile memory system, displays as are well known in the artfor operating such a system (see FIG. 5).

[0067] The dosimetry control system can operate in a “basic” mode ofoperation, which means that the physician utilizes a pre-selectedprogram to control to (i) the particular power level of laser source 25;(ii) the particular exposure duration of beams 35A-35 n. The power levelmay range from about 1 mJ to 100 mJ for the above-described beamdiameters, with a CW source or a rapidly pulsed source with pulse lengthranging from 1-1000 ms. As described above, the total duration oftreatment may range from about 1 second to 120 seconds.

[0068] Another operational mode, and a preferred mode, relates to use ofa feedback-controlled mode based on signals from thermal sensor(s) 57shown in FIGS. 6 & 8. In a first feedback-controlled mode, surfacetemperature at the anterior scleral surface 48 may be monitored bysensor array 57, such that dosimetry control system 55 may simplyterminate laser energy delivery upon a detected surface temperaturereaching a pre-set, for example any temperature in pre-selected from arange of about 42° C. to 55° C., each such temperature also optionallyincluding a pre-selectable time period ranging from about 1 ms to 30seconds. Thus, the detected temperatures at the anterior surface 48 ofthe sclera can be modeled (e.g., using Monte Carlo modeling as is knownin the art) to predict the temperature in the region of the meshwork Mfor creating the biostimulation temperature parameters described above.In another feedback controlled-operational mode, the dosimetry controlsystem 55 can be programmed to modulate power to one or more emitterlocations based on feedback from the sensor array 50.

[0069] In yet another operational mode of the invention, herein calledthe time-sequenced (or gated) operational mode, the dosimetry controlsystem 55 and more specifically the beam sequence controller 59 which isadapted to sequentially deliver laser energy at any given power levelbetween the individual emitter locations 31A-31 n. Such “sequential”delivery can provide energy delivery to only one particular spot in themeshwork M at a time, or any spot substantially remote from an adjacentspot (either in distance or time of delivery) to allow the thermalrelaxation time relative to a particular to spot to diffuse thetemperature within the absorbing medium. For example, the beam sequencecontroller 59 may randomly, or in a pre-set sequence, select only onesingle emitter to emit a beam at any moment in time thus sequencingbetween any adjacent or non-adjacent emitters; or controller 59 mayselect from 2 to n non-adjacent emitters to emit beam simultaneouslywhile sequencing between or among another single emitter or anycombination of emitters 31 a-31 n. By this beam delivery sequencingmeans, and thermal modeling as is known in the art such as Monte Carlomodeling, beam sequencing patterns can be developed as a function ofboth the thermal relaxation time about a beam's propagation and the heataborption characteristics of working face 30 to optimize thebiostimulative temperature elevation in the trabecular meshwork.

[0070] Specific features of the invention are shown in some drawings andnot in others, and this is for convenience only and any feature may becombined with another in accordance with the invention. Furthervariations will be apparent to one skilled in the art in light of thisdisclosure and are intended to fall within the scope of the appendedclaims.

What is claimed is:
 1. A method for delivering energy to trabecularmeshwork in a patient's eye, comprising: positioning a working face of amember in contact with a patient's sclera overlying the trabecularmeshwork; and delivering at least one laser beam through the memberwherein said at least one beam is transmitted transclerally to irradiatea region of said trabecular meshwork.
 2. The method of claim 1 whereinsaid at least one beam has a wavelength range from about of 1.30 μm to1.85 μm.
 3. The method of claim 1 further comprising the steps of:sensing a temperature of the sclera overlying the trabecular meshworkwith at least one sensor in said member to provide a signal; andmodulating or terminating the delivery of said at least one laser beamin response to said signal.
 4. The method of claim 3 further comprisingthe step of elevating the temperature of said trabecular meshwork to arange between about 40° C. to 55° C.
 5. A method for delivering energyto a patient's trabecular meshwork to treat glaucoma, comprising thesteps of: (a) placing a laser emitter in contact with a portion of thesclera of the patient's eye overlying the trabecular meshwork; (b)delivering laser energy from the emitter at a wavelength ranging betweenabout 1.30-1.40 μm or 1.55-1.85 μm; and (c) modulating the power level,pulse duration and pulse intervals of the laser energy to maintain thetemperature of the trabecular meshwork at less than about 60° C. (d)wherein said laser energy delivery causes substantially uniform thermaleffects in all layers of the trabecular meshwork.
 6. The method of claim5 wherein the laser emitter is carried in a contact surface of athermally conductive material having a surface area greater that about20 mm² thereby conducting heat away from surface sclera layers.
 7. Themethod of claim 5 further comprising the steps of sensing thetemperature of the sclera overlying the trabecular meshwork with atleast one sensor carried within the working face to provide a signal andmodulating the laser energy delivery in response to the signal.
 8. Amethod for delivering energy to a patient's trabecular meshwork to treatglaucoma, comprising the steps of: (a) placing a laser emitter incontact with a patient's eye wherein the axis of laser beam propagationis aligned with the trabecular meshwork; (b) delivering laser energyfrom the emitter at a selected wavelength; and (c) modulating the powerlevel, pulse duration and pulse intervals of the laser energy tomaintain the temperature of the trabecular meshwork at less than about60° C.; (d) wherein said laser energy delivery causes substantiallyuniform thermal effects in all layers of the trabecular meshwork.